Objective:

Congenital heart diseases (CHD) are often associated with thymus development disorders and immune dysfunctions. However, the features of thymocyte differentiation in cyanotic and acyanotic CHD remain unknown.

Materials and Methods:

We have analyzed the main thymocyte subsets depending on CD4 and CD8 co-expression, and the number of natural regulatory T-cells (nTreg) and invariant natural killer T-cells (iNKT) precursors in the co-cultures of thymocytes with thymic plasmacytoid (p) dendritic cells (DCs) in vitro, isolated from the thymus of children with acyanotic (without hypoxia) and cyanotic (with severe hypoxia) CHD.

Results:

In the thymocyte co-cultures with pDCs in cyanotic CHD, compared to acyanotic CHD, a decreased number of thymocytes expressing αβ chains of the T-cell receptor with CD4 and CD8 lower levels (CD4^loCD8^loαβTCR⁺), but the increased numbers of CD4hiCD8^-/loαβTCR⁺ cells were detected. The numbers of CD4CD8αβTCR+, CD4^hiCD8^hiαβTCR⁺, CD4^-/loCD8^hiαβTCR⁺ cells did not differ between cyanotic or acyanotic CHD. In cyanotic CHD in the thymocyte co-cultures with pDCs, the decreased number of CD4⁺CD25⁺FOXP3⁺ cells, nTreg precursors, was detected in comparison with acyanotic CHD. In cyanotic CHD, the number of CD3^hiVα24Jα18⁺ cells, iNKT precursors, in the thymocyte co-cultures with pDCs did not differ in comparison with acyanotic CHD. Hypoxia in cyanotic CHD increased the resistance to apoptosis of thymocytes in co-cultures with pDCs in comparison with acyanotic CHD.

Conclusion:

Thus, hypoxia affected the main CD4⁺ and CD8⁺ αβTCR T-cell subsets and the number of CD4⁺CD25⁺FOXP3⁺ cells in the thymocyte co-cultures with pDCs isolated from thymus of children with CHD.

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